Effect of Stimulators upon Human Hepatic Adenylate Cyclase Activity: A Tool of Nitroimidazole Cytotoxicity Assessment

Nitroimidazole is an antibiotic and radiosensitizer chemical with great potentials in imaging. The hepato-cytoxicity evaluation of nitroimidazole and possible energy status changes in liver cells due to its anti-inflammatory characteristics are crucial in tumor imaging and chemotherapy. Adenylate cyclase is key enzyme to cause energy imbalance leading to cytotoxicity. To evaluate energy status in hepatocytes and Kupffer cells, adenylate cyclase activities in isolated liver cells were compared in presence of stimulators. To evaluate the effect of effectors on adenylate cyclase in cultured hepatocyte cells, adenylate cyclase enzyme was stimulated by different GITP, GTP, progesterone and nitroimidazole effectors. In cultured Kupffer cells, prostaglandin E~2~ and F~2[alpha]~ were used as effectors. The results showed that nitroimidazole decreased adenylate cyclase specific activity in dose-dependent manner after pre-incubation of hepatocytes with the nitroimidazole in medium. Nitroimidazole stimulated adenylate cyclase activities in hepatocytes were mediated by cAMP and determined by cAMP mesurement. The stimulatory effect of nitroimidazole on adenylate cyclase was independent of the GTP presence in the assay system perhaps due to a direct effect on the catalytic subunit of adenylate cyclase enzyme. In addition, basal cAMP generation in hepatocyte cells was efficiently suppressed by the nitroimidazole. In conclusion, nitroimidazole exhibits direct effect on the catalytic subunit of the adenylate cyclase system. The adenylate cyclase was hormone sensitive in liver cells.